title: Seven-tesla magnetic resonance imaging accurately quantifies intratumoral uptake of therapeutic nanoparticles in the McA rat model of hepatocellular carcinoma: preclinical study in a rodent model.
abstract: OBJECTIVE
  After inducing McA tumors in Sprague-Dawley rats (McA-SD), the following hypotheses were tested: first, that hypervascular McA tumors grown in Sprague-Dawley rats provide a suitable platform to investigate drug delivery; and second, that high-field MRI can be used to measure intratumoral uptake of DOX-SPIOs.
  
  
  METHODS
  McA cells were implanted into the livers of 18 Sprague-Dawley rats. In successfully inoculated animals, 220-μL DOX-SPIOs were delivered to tumors via the intravenous or intra-arterial route. Pretreatment and posttreatment T2*-weighted images were obtained using 7-T MRI, and change in R2* value (ΔR2*) was obtained from mean signal intensities of tumors in these images. Tumor iron concentration ([Fe]), an indicator of DOX-SPIO uptake, was measured using mass spectroscopy. The primary outcome variable was the Pearson correlation between ΔR2* and [Fe].
  
  
  RESULTS
  Tumors grew successfully in 13 of the 18 animals (72%). Mean (SD) maximum tumor diameter was 0.83 (0.25) cm. The results of phantom studies revealed a strong positive correlation between ΔR2* and [Fe], with r = 0.98 (P < 0.01). The results of in vivo drug uptake studies demonstrated a positive correlation between ΔR2* and [Fe], with r = 0.72 (P = 0.0004).
  
  
  CONCLUSIONS
  The McA tumors grown in the Sprague-Dawley rats demonstrated uptake of nanoparticle-based therapeutic agents. Magnetic resonance imaging quantification of intratumoral uptake strongly correlated with iron concentrations in pathological specimens, suggesting that MRI may be used to quantify uptake of iron-oxide nanotherapeutics.
authors.affiliation: From the Departments of *Radiology, and †Biomedical Engineering, ‡Feinberg School of Medicine, and §Robert H. Lurie Comprehensive Cancer Center, Northwestern University, Chicago, IL; and ∥Department of Radiology and Radiological Sciences, Vanderbilt University Medical Center, Nashville, TN.
authors.forename: Patrick D
authors.initials: PD
authors.lastname: Tyler
authors.forename: Joseph L
authors.initials: JL
authors.lastname: McDevitt
authors.forename: Alexander Y
authors.initials: AY
authors.lastname: Sheu
authors.forename: Jodi
authors.initials: J
authors.lastname: Nicolai
authors.forename: Daniele
authors.initials: D
authors.lastname: Procissi
authors.forename: Ann B
authors.initials: AB
authors.lastname: Ragin
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Lewandowski
authors.forename: Riad
authors.initials: R
authors.lastname: Salem
authors.forename: Andrew C
authors.initials: AC
authors.lastname: Larson
authors.forename: Reed A
authors.initials: RA
authors.lastname: Omary
mesh_terms: D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000493:pharmacokinetics; D003911:Dextrans; D004317:Doxorubicin / Q000493:pharmacokinetics*; D006801:Humans; D008114:Liver Neoplasms, Experimental / Q000188:drug therapy* / Q000378:metabolism* / Q000473:pathology; D008279:Magnetic Resonance Imaging / Q000379:methods*; D058185:Magnetite Nanoparticles; D008297:Male; D053758:Nanoparticles / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014018:Tissue Distribution; D016896:Treatment Outcome
chemical_list: D000903:Antibiotics, Antineoplastic; D003911:Dextrans; D058185:Magnetite Nanoparticles; C097921:ferumoxtran-10; D004317:Doxorubicin